Information on migraine drugs in commonly available Indian drug information sources - Whether we satisfied the community needs?

Drug information can be obtained from various drug information sources that were available as government (National Formulary of India [NFI]; Central Drugs Standard Control Organization [CDSCO]), as well as commercial documents (Current Index of Medical Specialties [CIMS] and Monthly Index of Medical Specialties [MIMS]). Irrational drug usage may happen due to wide variation in the information available in these sources. In this study, we tried to assess these variations in a sample of drugs for the acute-specific management of migraine with ergot and Triptans antimigraine drugs in drug information sources such as NFI, CIMS, MIMS, and CDSCO. Scoring was done for various drug information based on the completeness of information about drugs used in acute-specific management of migraine. The scores for the completeness of drug information about the selected antimigraine drugs are 18.37% for CIMS (Ergotamine, Sumatriptan, Rizatriptan, and Zolmitriptan), 21.1% for NFI (Dihydroergotamine, Sumatriptan), 72.79% for MIMS (Ergotamine tartrate, Sumatriptan, Rizatriptan, Naratriptan, zolmitriptan, Almotriptan) and 21.77% for CDSCO (Ergotamine tartrate, Sumatriptan, Rizatriptan, Naratriptan, Zolmitriptan, eletriptan and almotriptan). The information for the antimigraine drugs available from various sources found to so much deficient. Necessary steps need to be taken in case of government public or hard documents to streamline drug information available with them as well the commercial documents as to provide reliable drug information uniformly for promoting rational use of the drug.

Introduction

Migraine is a complex and still a debatable neurovascular disorder that is on the rise globally, affecting patients of all ages. Various drugs are available for acute and chronic management, but migraine appears to be a chronic and progressive condition, with 5.1% of patients ultimately becoming refractory to drugs. Drugs for managing migraine are broadly categorized into two classes: drugs for treating acute migraine and those for preventing migraines. For managing acute migraines, adequate dosage, route, and timing of drug administration are the key factors.[1] A drug should be properly prescribed in its patient-needed dose, proper interval of time and duration. These are important in treating a case of confirmed diagnosis. This is an important part of a rational prescription. Irrational and inappropriate usage of drugs will lead to proper clinical response and possible serious type of adverse drug reactions (ADRs).[2] In order to prescribe, the knowledge of unbiased authenticated drug-related information helps in the rational use of drugs for treatment. Knowledge of drug information can be obtained from various sources of information readily available. The most important and commonly used drug information resources are the National Formularies government (National Formulary of India [NFI]), commercial drug compendia such as the Current Index of Medical Specialties (CIMS), Monthly Index of Medical Specialities (MIMS), Package inserts (PIs) of drugs and or textbooks of pharmacology/internal medicines.[34]

These drug resources should contain information that compiles the uniformity, reliability, reproducibility and it should conform to the regulator label of a particular country. Every country has their own approved indication/s of the drug as per the geographical distribution and clinical response in their country that was being approved by their respective regulators.[56] In case of India, it is the Central Drugs Standard Control Organization (CDSCO) approving all indications of all the approved essential drugs being a Government of India body.[7]

Among this except for CDSCO, all other resources were available as hard copies. CIMS were available both in hard circulation as well as online information resources. The management of migraine is important as it hampers daily routine activities and the available drugs in different classes have a different ADR profile. Hence, we planned the present study to assess the variation if any persist in the drugs used in migraine, acute management with respect to various parameters of drug information. The objective of the study is to compare the drug information on the management of acute migraine attacks by Triptans and ergotamine available in different drug information sources and to identify any gross variations in the drug information among various drug information sources.

Materials and Methods

The study was carried out in the All India Institute of Medical Sciences, Raipur. This is a descriptive study conducted only due approval from the Institute Ethics Committee (Proposal No. AIIMSRPR/IEC/2019/282). We have analyzed the information available in various drug information sources about drugs used in the management of migraine. The drugs commonly used in migraine are nonsteroidal anti-inflammatory drugs, ergotamine, and dihydroergotamine, triptans, beta-blockers, tricyclic antidepressants, calcium channel blockers, and adjutants. Among these, we have taken the drugs used in acute-specific management of migraine mainly ergotamine and triptans. We assessed the information from the drug information sources such as NFI-2016 NFI, CIMS India, MIMS, and approved drugs from CDSCO website.[8] The sections that were examined are indications (I), dosage (D), contraindication (CI), special precautions (SPs), ADR, drug interaction (DI), and pregnancy category (P). The information was extracted from the above sources, tabulated and scores were assigned for the completeness of drug information. The scores for assessing the completeness of the information were given as 0, 1, 2, and 3 where 0 is for incorrect/not available, 1 is for Partially correct, 2 is for correct and insufficient and 3 is for correct/complete/sufficient. The completeness is authenticated by experts and from the standard textbook of pharmacology and clinical pharmacology. Also, we considered the absence of drug in particular source as score 0 for comparison.

Statistical analysis

The data were presented as scores with a maximum score of 3 for each of the seven parameters considered and hence the maximum score for each drug was 21. The final comparison between all the sources of drug information was based on this scoring. The scores were also given to drug information sources with a maximum score being 147 based on the completeness of information on the 7s selected drugs from CDSCO.

Results

The first part of the analysis started with the collection of various drug information sources. As planned, we analyzed information from current (NFI), (2016) CIMS (January–Mar 2019), MIMS (April 2019), and CDSCO (currently updated as on date). The CDSCO-approved drugs are taken for analysis for completeness [Figure 1]. In CIMS, the antimigraine drugs that are mentioned are shown in Figure 2. Among these, the drugs for the management of acute attack of migraine are ergotamine, sumatriptan, rizatriptan, and zolmitriptan. The partial information is seen with indication and dose of sumatriptan, rizatriptan, and zolmitriptan. There is no information on all other parameters mentioned above for the drug in CIMS. On the contrary, the CIMS online [Figure 2] resources provided 100% information for rizatriptan, zolmitriptan, eletriptan, naratriptan, and almotriptan. Regarding indication and dosage, the information is correct but insufficient in case of ergotamine and sumatriptan.

Figure 1

Flowchart. NFI=National Formulary of India, CDSCO=Central Drugs Standard Control Organization, CIMS=Current Index of Medical Specialties, MIMS=Monthly Index of Medical Specialties

Figure 2

Comparison of scores in various sources for available drugs. NFI=National Formulary of India, CDSCO=Central Drugs Standard Control Organization, CIMS=Current Index of Medical Specialties, MIMS=Monthly Index of Medical Specialties

In NFI, the drugs for the management of acute attack of Migraine are dihydroergotamine and sumatriptan [Figure 2]. On analyzing the information about these drugs, we observed that the dosage information is insufficient for dihydroergotamine and sumatriptan. The parameters CI, SP, ADR information of sumatriptan is inadequate and the parameter DI information is not mentioned for both the drugs.

In MIMS [Figure 2], the antimigraine drugs that are mentioned are propranolol, valproic acid, naratriptan, flunarizine, rizatriptan, sumatriptan, and ergotamine tartrate in combination with delladonna extract, caffeine and paracetamol, paracetamol in combination with metoclopramide. Among these, the drugs used for the management of acute attacks of Migraine are ergotamine tartrate, sumatriptan, rizatriptan, naratriptan, almotriptan, and zolmitriptan. On careful analysis, we observed that the dosage information of sumatriptan is insufficient and there is no mention of pregnancy category information for any drug.

In CDSCO [Figure 2], there is no information regarding CI, SP, ADR, DI, pregnancy category.

The scores for the completeness of drug information about the selected antimigraine drugs are 18.37% for CIMS, 21.1% for NFI, 72.79% for MIMS, and 21.77% for CDSCO. For CIMS online it is 97.3% complete information are provided [Figure 3].

Figure 3

Comparison on the percentage of completeness. NFI=National Formulary of India, CDSCO=Central Drugs Standard Control Organization, CIMS=Current Index of Medical Specialties, MIMS=Monthly Index of Medical Specialties

Discussion

Off-label use of a drug, however, it may be irrational or unscientific that should be tested with randomized control trial.[9] In order to promote drug rationale, it is important that relevant information about any drug on its approved indication, dosage, CI, SP, ADR, DI, pregnancy category should be clearly and almost readily available to the physician and the general practitioner. For the purpose common sources like (NFI), PI, commercially published drug compendia such as MIMS and CIMS should be available with the physician/practitioner for reference and prescription.[34] Hence, the information available in such sources should confirm uniformity with the labeling information that was being approved by the drug regulator of that country and ease in decision making irrespective of the source (s) of information.

It was observed that no information about parameters such as CI, SP, ADR pregnancy category is mentioned on the CDSCO website. Regarding the dosage, there is insufficient information. The NFI being a document of the huge reference by the entire educational institute and rarely by the general practitioner contained information of only 2 drugs. It is always mandated to include the drugs mentioned in the National List of Essential Medicines (NLEM) and some other commonly used drugs.[10] Even though the drug in NLEM and NFI contains only few drugs, as per NLEM 2015, dihydroergotamine has been removed and sumatriptan is added but NFI contains information on both the drugs. The information regarding the NLEM listed drug sumatriptan covered only 66.66% and it is the same with dihydroergotamine with 80.95%. In commercially available MIMS, it was observed to contain the essential information but the information on the pregnancy category is totally absent. This is being an important parameter as migraine is mostly affecting the female and in the reproductive age groups. Even though it provides more than 70% complete information it is noteworthy to be mentioned that their hardcopy supply to the end-users was stopped after April 2019 issues with a proposal for online resources. Even though the online CIMS contains more than 95% of the complete information of the drugs, our study focused on the resources available hard copies except for CDSCO information. Still, we have included in the comparisons.

In general, PIs contain maximum information that was not mentioned on the regulators resources. However, there is always a concern that these inserts are not seen along with drug packages and it is neither regulated by the authorities and or made as an mandatory as a part.[11] Here, in our analysis in addition to the above resources, we tried to randomly get PI s of the ergot and triptan drugs available for usage in India. However, it came as a surprise as we could not able to get the PIs from the close by pharmacies. The Inserts provide the needed and essential information whenever available if a new drug is introduced in the country. However, this is not seen in our study for the sample of antimigraine drugs. The purpose of looking into the PIs is that if there is a vast difference in the information it may lead to the irrational off-label drug use.[121314]

On the basis of the aforementioned facts, it can be clearly inferred that the CDSCO website does not contain the all the information about any of the commonly used drugs even though these drugs are marketed in India. This may be due to the fact that they purely focused on approved indication and the banned drug information. However, it may be desired and mandate for the regulatory board to provide all the information for the end-users with full authentication.

This study highlights the variations or deficiencies in drug information parameters available in the above-mentioned sources by taking a representative sample of antimigraine drugs. To the best of our knowledge in case of migraine drug, this study is the first such attempt to look into the information deficiency of a drug used in neurospecialty. The drugs selected were identified on the basis of the drugs that are approved to use in India for the management of acute attacks of migraine. The group ergot and triptans were identified on the basis of the physician opinion and their prescription pattern in various specialty hospitals and in our setting.

Conclusion

The information about antimigraine drugs available from various sources showed a major deficiency and there is a need that should be seriously taken care by the resources. The resources that are under the government of India should be mandated to contain all the information when a drug is approved in India. Even though the government focus is on the essential medicine and their information, the era of information technology should be implemented to provide the maximum information regarding all the approved drugs in India especially that deals the specialty areas.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.